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Journal of Pharmacology And Experimental Therapeutics, Vol. 115, Issue 1, 68-73, 1955
Copyright © 1955 by American Society for Pharmacology and Experimental Therapeutics

INHIBITION OF DRUG METABOLIC PATHWAYS BY THE POTENTIATING AGENT, 2,4-DICHLORO-6-PHENYL-PHENOXYETHYL DIETHYLAMINE

J. R. Fouts 1 and Bernard B. Brodie 1

1 The Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Public Health Service, U. S. Department of Health, Education, and Welfare, Bethesda, Maryland

2, 4-Dichloro-6-phenylphenoxyethyl diethylamine HBr (Lilly 18947), in doses devoid of sedative activity, prolongs the hypnotic activity of hexobarbital in mice by inhibiting its rate of biotransformation.

Lilly 18947 inhibits enzyme systems present in liver microsomes which oxidize the sidechain of hexobarbital, dealkylate aminopyrine, deaminate amphetamine, cleave the ether linkage of codeine, hydroxylate acetanilide and conjugate morphine. These biochemical pathways are also blocked by beta-diethylaminoethyldi-phenyipropylacetate HCl (SKF 525-A) and diphenylpropylacetic acid (SKF acid).

It is probable that, despite their dissimilarity in structure, Lilly 18947 and the SKF compounds act by a similar mechanism.

Submitted on May 4, 1955






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Copyright © 1955 by the American Society for Pharmacology and Experimental Therapeutics.